Bordetella bronchiseptica and Bordetella pertussis are closely related respiratory pathogens that evolved from a common bacterial ancestor. While B. bronchiseptica has an environmental reservoir and mostly establishes chronic infections in a broad range of mammals, B. pertussis is a human-specific pathogen causing acute pulmonary pertussis in infants and whooping cough illness in older humans. Both species employ a type III secretion system (T3SS) to inject a cytotoxic BteA effector protein into host cells. However, compared to the high BteA-mediated cytotoxicity of B. bronchiseptica, the cytotoxicity induced by B. pertussis BteA (Bp BteA) appears to be quite low and this has been attributed to the reduced T3SS gene expression in B. https://www.selleckchem.com/Proteasome.html pertussis. We show that the presence of an alanine residue inserted at position 503 (A503) of Bp BteA accounts for its strongly attenuated cytotoxic potency. The deletion of A503 from Bp BteA greatly enhanced the cytotoxic activity of B. pertussis B1917 on mammalian HeLa cells and expression of Bp BteAΔA503 was highly toxic to Saccharomyces cerevisiae cells. Vice versa, insertion of A503 into B. bronchiseptica BteA (Bb BteA) strongly decreased its cytotoxicity to yeast and HeLa cells. Moreover, the production of Bp BteAΔA503 increased virulence of B. pertussis B1917 in the mouse model of intranasal infection (reduced LD50) but yielded less inflammatory pathology in infected mouse lungs at sublethal infectious doses. This suggests that A503 insertion in the T3SS effector Bp BteA may represent an evolutionary adaptation that fine-tunes B. pertussis virulence and host immune response.The host innate immune system has developed elegant processes for the detection and clearance of invasive fungal pathogens. These strategies may also aid in the spread of pathogens in vivo, although technical limitations have previously hindered our ability to view the host innate immune and endothelial cells to probe their roles in spreading disease. Here, we have leveraged zebrafish larvae as a model to view the interactions of these host processes with the fungal pathogen Candida albicans in vivo. We examined three potential host-mediated mechanisms of fungal spread movement inside phagocytes in a "Trojan Horse" mechanism, inflammation-assisted spread, and endothelial barrier passage. Utilizing both chemical and genetic tools, we systematically tested the loss of neutrophils and macrophages and the loss of blood flow on yeast cell spread. Both neutrophils and macrophages respond to yeast-locked and wild type C. albicans in our model and time-lapse imaging revealed that macrophages can support yeast spread in a "Trojan Horse" mechanism. Surprisingly, loss of immune cells or inflammation does not alter dissemination dynamics. On the other hand, when blood flow is blocked, yeast can cross into blood vessels but they are limited in how far they travel. Blockade of both phagocytes and circulation reduces rates of dissemination and significantly limits the distance of fungal spread from the infection site. Together, this data suggests a redundant two-step process whereby (1) yeast cross the endothelium inside phagocytes or via direct uptake, and then (2) they utilize blood flow or phagocytes to travel to distant sites.Resettlement, as a major imperial policy in the Inca empire, appears to have been a widespread mechanism for labor mobilization and the dismantling of rebellions. While multiple ethnohistorical references exist regarding resettlement in the central Andes, the extent of this policy in the imperial provinces is still unknown, especially in cases of economic intensification that might have required more labor force. The δ18O isotope is a good proxy for human mobility when comparing the childhood isotopic signature in the teeth enamel and the local water signature at the place of death. If applied to the study of an archaeological sequence, we can observe the expansion or reduction of a population's displacement within a territory, if they received foreigners, and in general, how their social interaction and networks changed over time. In a marginal provincial setting of the Inca empire, such as Copiapó valley in Chile, the study of δ18O isotope can enable us to observe if the alleged economic intensification in metallurgical production implied the massive arrival of foreign populations. Significantly, the Late Horizon does not evidence a great change in terms of mobility, compared to previous periods in Copiapó valley. Thus, the isotopic evidence can more clearly illuminate the social and political dynamics of an imperial provincial setting, where economic activities demanded by the Inca state were mainly carried out by the local labor force.Mountainous freeways with high bridge and tunnel ratios are a new type of road that rarely contain many special road sections formed by various structures. The crash characteristics of the road are still unclear, but it also provides conditions for studying how various road environments affect traffic. In view of the various structures and differences in the driving environments, a scenario-based discretization method for such a road was established. The traffic-influence areas of elementary and composite structures were proposed and defined. Actual data were analyzed to investigate the crash patterns in an entire freeway and in each special section through statistical and comparative research. The results demonstrate the applicability and validity of this method. The crash rates were found to be the highest in interchange and service areas, lower in ordinary sections, and the lowest in tunnels, being mostly attributed to collisions with fixtures. The crash severity on bridges and bridge groups was significantly higher than that on the other types of road sections, being mostly attributed to single-vehicle crashes. The annual average daily traffic and driving adaptability were found to be related to crashes. The findings shed some light on the road design and traffic management implications for strengthening the traffic safety of mountainous freeways.This study aims to examine associations between spousal communication about contraception and ever use of modern contraception, overt modern contraceptive use (with husband's knowledge), and covert modern contraceptive use (without husband's knowledge) among adolescent wives and their husbands in Niger.
Cross-sectional data, from the Reaching Married Adolescents Study, were collected from randomly selected adolescent wives (ages 13-19 years) and their husbands from 48 randomly selected villages in rural Niger (N = 1,020 couples). Logistic regression models assessed associations of couples' reports of spousal communication about contraception with wives' reports of contraception (overall, overt, and covert).
About one-fourth of adolescent wives and one-fifth of husbands reported spousal communication about contraception. Results showed couples' reports of spousal communication about contraception were positively associated with ever use of modern contraception. Couples' reports of spousal communication about contraception were negatively associated with covert modern contraceptive use compared to overt use.